Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity

Extracellular interaction between programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) leads to tumour-associated immune escape. Here we show that the immunosuppression activity of PD-L1 is stringently modulated by ubiquitination and N-glycosylation. We show that glycogen synthase kinase 3β (GSK3β) interacts with PD-L1 and induces phosphorylation-dependent proteasome degradation of PD-L1 by β-TrCP. In-depth analysis of PD-L1 N192, N200 and N219 glycosylation suggests that glycosylation antagonizes GSK3β binding. In this regard, only non-glycosylated PD-L1 forms a complex with GSK3β and β-TrCP. We also demonstrate that epidermal growth factor (EGF) stabilizes PD-L1 via GSK3β inactivation…

• BC
  Breast Cancer Research Foundation
• DK
  Deutsches Krebsforschungszentrum
• NB
  National Breast Cancer Foundation
• NR
  National Research Foundation

  Award: 2011-0030001
• MO
  Ministry of Science, ICT and Future Planning

  Awards: 2011-0030001, NRF-2011-357-C00140
• NR
  National Research Foundation of Korea

  Awards: NRF-2011-357-C00140, 2011-0030001
• CM
  China Medical University Hospital
• CM
  China Medical University
• NI
  National Institutes of Health

  Awards: CA109311, R01 CA109311, CA099031, CA016672, CCSG CA016672
• UO
  University of Texas MD Anderson Cancer Center

  Awards: CCSG CA016672, CA016672